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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00110266
Other study ID # CICL670AUS03
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date July 25, 2005
Est. completion date March 28, 2008

Study information

Verified date July 2021
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.


Description:

Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.


Other known NCT identifiers
  • NCT00343837

Recruitment information / eligibility

Status Completed
Enrollment 176
Est. completion date March 28, 2008
Est. primary completion date March 28, 2008
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Male or female patients with low or intermediate (INT-1) risk MDS - Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO). - Age greater than or equal to 18 years - Availability of transfusion records for the 12 weeks prior to registration - A lifetime minimum of 30 previous packed red blood cell transfusions - Availability of at least three CBC values (pretransfusion) during the 12 weeks prior to registration - Serum Ferritin: For entry into the screening period, serum ferritin = 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year. Serum ferritin = 1000 ng/mL at screening via the central lab. - Life expectancy = 6 months - Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months) - Able to provide written informed consent Exclusion Criteria: - Serum creatinine above the upper limit of normal - Alanine aminotransferase (ALT) > 500 U/L during screening - Clinical or laboratory evidence of active Hepatitis B or C - Urinary protein/creatinine ratio > 0.5 mg/mg - History of HIV positive test result (ELISA or Western blot) - Eastern Cooperative Oncology Group (ECOG) Performance Status > 2 - Patients with uncontrolled systemic hypertension - Unstable cardiac disease not controlled by standard medical therapy - Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation - Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment - Pregnancy or breast feeding - Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days - Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug - History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

Study Design


Intervention

Drug:
Deferasirox
20 mg/kg/day over one year in patients with MDS

Locations

Country Name City State
Canada Novartis Investigative Site Hamilton Ontario
Canada Novartis Investigative Site Montreal Quebec
Canada Novartis Investigative Site Montreal Quebec
Canada Novartis Investigative Site Toronto Ontario
Canada Novartis Investigative Site Toronto Ontario
Canada Novartis Investigative Site Vancouver British Columbia
United States NMOHC Albuquerque New Mexico
United States Cabrini Center for Cancer Care/Christus St. Frances Cabrini Hospital Alexandria Louisiana
United States Arlington Fairfax Hematology Oncology PC Arlington Virginia
United States Cancer Care of WNC Asheville North Carolina
United States Emory University School of Medicine/Winship Cancer Institute Atlanta Georgia
United States Rocky Mountain Cancer Centers Aurora Colorado
United States St. Agnes HealthCare Baltimore Maryland
United States Univ of Alabama Birmingham Birmingham Alabama
United States Roswell Park Cancer Center Buffalo New York
United States Novartis Investigative Site Chicago Illinois
United States University of Chicago Hospital Chicago Illinois
United States The Cleveland Clinic Foundation Cleveland Ohio
United States The Ohio State University Columbus Ohio
United States Bay Area Cancer Research Group Concord California
United States City of Hope National Medical Center Duarte California
United States The Cancer Center at Hackensack University Hackensack New Jersey
United States Straub Clinic and Hospital Honolulu Hawaii
United States Baylor/The Methodist Hospital Houston Texas
United States Mayo Clinic Jacksonville Florida
United States University of Kansas Medical Center Kansas City Kansas
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States University of Kentucky College of Medicine, Markey Cancer Center Lexington Kentucky
United States Cedars-Sinai Medical Center, UCLA School of Medicine Los Angeles California
United States UCLA Medical Center Los Angeles California
United States The West Cancer Clinic Memphis Tennessee
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Novartis Investigative site Nashville Tennessee
United States Oncology Hematology West, PC Omaha Nebraska
United States Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center Philadelphia Pennsylvania
United States Mayo Clinic Phoenix Arizona
United States Western Pennsylvania Hospital Cancer Institute Pittsburgh Pennsylvania
United States Novartis Investigative Site Portland Oregon
United States Mayo Clinic Rochester Minnesota
United States Rochester General Hospital/Lipson Cancer and Blood Center Rochester New York
United States The Center for Cancer Care & Research (TCCCR) Saint Louis Missouri
United States Utah Cancer Specialists Salt Lake City Utah
United States UCSF San Francisco California
United States UCSF San Francisco California
United States Novartis Investigative Site Southfield Michigan
United States Novartis Investigative Site Spokane Washington
United States Wake Forest UniversitComprehensive Cancer Center Winston-Salem North Carolina
United States Rush Cancer Institute Univ. of Massachussets Medical Center Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

List AF, Baer MR, Steensma DP, Raza A, Esposito J, Martinez-Lopez N, Paley C, Feigert J, Besa E. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012 Jun 10;30(17 — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Reporting Adverse Events Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. up to 53 Weeks
Secondary Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53). From Baseline to Weeks 13, 25, 37 and 53
Secondary Change in Labile Plasma Iron (LPI) LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 µM Fe From Baseline to Weeks 13, 25, 37 and 49
Secondary Directly Chelatable Iron (DCI) The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. From Baseline to Weeks 13, 25, 37 and 49
Secondary Total Iron Levels Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed. From Baseline to Weeks 13, 25, 37, 49 and 53
Secondary Serum Transferrin Levels Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed. From Baseline to Weeks 13, 25, 37, 49 and 53
Secondary Transferrin Saturation Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months. From Baseline to Weeks 13, 25, 37, 49 and 53
Secondary Transfusion Requirements Number of participants receiving transfusions, the summarized during the study. up to 1 year
Secondary Frequency of Hematologic Improvement During the Study Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as:
Erythroid response (pretreatment, <11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,<100x10^9/L): If starting with >20x10^9/L platelets: absolute increase 30x10^9/L, Increase from baseline <20 x10^9/L to >20x10^9/L and by =/> 100%; Neutrophil response (pretreatment, <1.0x10^9/L): =/> 100% increase & absolute increase >0.5x10^9/L; Progression or relapse after HI: At least 1 of the following: =/>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.
up to 1 year
Secondary Trough Plasma Deferasirox Concentration The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method. At Week 13, 25, 37 and 49
Secondary Treatment Compliance to Deferasirox Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits. up to 1 year
Secondary The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant. up to Week 13 (Month 3)
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